Vision begins when light is converted to an electrical signal in the photoreceptors. Increases in light decrease release of the neurotransmitter, glutamate, from cone and rod photoreceptor terminals, and decreases in light increase its release. These changes in synaptic glutamate concentration are detected by two classes of bipolar cells that then transmit the signal vertically through the retinal circuit to the ganglion cells. The neurotransmitter changes also are detected by horizontal cells that provide lateral transmission in the form of feedback and feedforward inhibition. There are two classes of bipolar cells, hyperpolarizing (HBCs) and depolarizing (DBCs). HBCs utilize ionotropic glutamate receptors and hyperpolarize in response to a light flash. DBCs utilize a metabotropic glutamate receptor, mGluR6, that signals to TRPM1, depolarizing in response to a light flash. Defects in transmission in DBCs results in complete congenital stationary night blindness (cCSNB). Mutations in GRM6, NYX, TRPM1 and GPR179 cause cCSNB. The mechanism by which mGluR6 signals TRPM1 is largely unknown. The long term goal of this project is study the molecular interactions between two recently discovered retinal components, GPR179 and Cav1.1, and the other DBC signal transduction components. The specific aims are: 1) Determine the role of GPR179 in DBC signalplex assembly/function, 2) determine the role of Cav1.1 in DBC signalplex assembly and function, and 3) Determine functional and trafficking interdependence of DBC signalplex components. At the completion of this project, we will have characterized the function of newly discovered proteins (GPR179 and Cav1.1) critical to signal transmission in DBCs. Further, we will have identified new candidate genes for congenital stationary night blindness.